PROVISION: Perioperative Vitamin C to Reduce Persistent Pain After Total Knee Arthroplasty
Study Details
Study Description
Brief Summary
Phase II Multicentre, pilot, parallel-group, blinded, 1:1 randomized controlled trial to determine the feasibility of conducting a larger definitive trail of using vitamin C to reduce persistent pain in patients undergoing total knee arthroplasty surgery.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PROVISION is a multicentre, pilot, parallel-group, blinded, randomized controlled trial of 100 patients undergoing total knee arthroplasty surgery. Consented eligible patients will be randomized to receive vitamin C: 2000 mg taken orally within 4 hours of the start of surgery, followed by 500 mg of vitamin C taken twice daily from post-operative day 1 to day 56 (8 weeks). Patient in the control group will receive placebo lactose monohydrate capsules. Study medications will be prepared to look similar and labelled as per regulatory requirements. Patients will follow up on post-operative days 1-3, weeks 2,4,6, and 8 post-operatively, and at 3- and 12-months post-operatively to report on pain, opioid and analgesic consumption, medication adherence, adverse events, functional, mood, and quality of life outcomes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intervention Preoperative Vitamin C capsules |
Drug: Vitamin C
Drug: Patients in the intervention group will receive 2g Vitamin C orally within 4 hours of the start of the surgery followed by 500 mg of Vitamin C to be taken orally twice a day from post-op day1 to day 56.
Other Names:
|
| Placebo Comparator: Placebo Preoperative placebo capsules |
Drug: Placebo
Drug: Patients in the placebo group will receive identical placebo capsules taken orally within 4 hours of the start of the surgery followed by placebo capsules taken orally twice a day from post-op day 1 to day 56.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Study will determine feasibility of enrolling, recruiting, and follow-up with patients. [12 months]
The study will assess the feasibility of enrolling, recruiting, and following-up with patients undergoing a primary total knee arthroplasty (TKA) through active monitoring of recruitment/enrollment rates on a monthly basis for a total of one year using excel trackers. The follow-up rate of patients will be assessed at 12 months based on completion of all 12 month questionnaires.
- Clinical site compliance [12 months]
Clinical site compliance with trial protocol will be determined based on number of protocol deviations at each site as logged on the deviation logs. This will be assessed on a monthly basis for a full year to maintain active monitoring of compliance.
- Resource Assessment [12 months]
This pilot study will help determine the resources required for larger definitive trial based on critical analysis of recruitment trackers to assess time spent on recruitment/enrollment.
Secondary Outcome Measures
- Prevalence of persistent pain [3 months and 12 months]
Pain intensity measured using 0-10 Numeric Rating Scale (NRS) scale at rest and movement
- Qualities and characteristics of persistent pain [3 months and 12 months]
Pain qualities measured using the 0-10 scale of the Short Form McGill Pain Questionnaire 2 (SF-MPQ-2)
- Persistent Neuropathic Pain [3 months and 12 months]
Neuropathic pain assessed on a binary scale of Yes or No using the Douleur Neuropathique 4 (DN4) symptoms interview
- Acute and chronic analgesic consumption [Day of surgery, post-operative day 1-3, 3 months, and 12 months]
Analgesic and oral morphine-equivalent opioid consumption
- Development of Complex Regional Pain Syndrome (CRPS) [3 months and 12 months]
Presence of CRPS measured by a physical assessment of sensory, vasomotor, sudomotor/edema, and motor/tropic categories using the Budapest Criteria
- Physical function [3 months and 12 months]
Patient reported outcome measure to assess level of function, daily living activities and their affect on pain measured by answering 12 questions using the Oxford Knee Score (OKS)
- Emotional functioning [3 months and 12 months]
Patients emotional functioning measured on a scale of 1-5 using the Profile of Mood States (POMS)
- Postoperative cognitive impairment [3 months]
Assessment of different cognitive domains such as attention, concentration, memory, language, conceptual thinking, calculations, and orientation out of a total score of 22 using Montreal Cognitive Assessment - Blind (MoCA-BLIND)
- Patient Satisfaction [3 months and 12 months]
Assessment of patient satisfaction with surgery on scale of 0-100
- Quality of life assessment [3 months and 12 months]
Patient reported assessment of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression on a scale of level 1 - level 5 using the EuroQol 5-dimension 5-level (EQ-5D-5L)
- Adverse events [3 months and 12 months]
Monitored as a secondary safety outcome using an assessment of follow-up visits for drug related adverse events and passive surveillance of clinical notes
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients >18 years old
-
Undergoing a unilateral or bilateral primary total knee arthroplasty for advanced osteoarthritis of the knee
Exclusion Criteria:
-
TKA for infection (septic joint), fracture, ankylosing spondylitis, lupus, or psoriatic arthritis
-
History of kidney stones, acute or chronic renal failure, hemochromatosis, or glucose-6-phosphate deficiency
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Unlikely to comply with follow-up (e.g., no fixed address, plans to move out of town)
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Language difficulties that would impede valid completion of questionnaires
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Planned staged bilateral TKA
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Treating surgeon deems patient inappropriate for inclusion in trial
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Any allergy or sensitivity to milk
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Pregnant or planning to become pregnant during the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sunnybrook - Holland Centre | Toronto | Ontario | Canada | M4Y 1H1 |
| 2 | Mount Sinai Hospital | Toronto | Ontario | Canada | M5G 1X5 |
| 3 | Toronto Western Hospital | Toronto | Ontario | Canada | M5T 2S8 |
Sponsors and Collaborators
- Mount Sinai Hospital, Canada
- Canadian Institutes of Health Research (CIHR)
- The Arthritis Society, Canada
Investigators
- Principal Investigator: James Khan, MD, Mount Sinai Hospital; Department of Anesthesia and Pain Medicine
- Principal Investigator: Raman Mundi, MD, Holland Orthopedic and Arthritic Centre
- Principal Investigator: Harman Chaudhry, MD, Holland Orthopedic and Arthritic Centre
- Principal Investigator: Jesse Wolfstadt, MD, Mount Sinai Hospital; Department of Surgery
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CTO: 4371